Ligands for alpha-7 nicotinic acetylcholine receptors and methods of treating neurological and inflammatory conditions

Abstract

Compounds are provided which bind to an allosteric site on the mammalian alpha-7 nicotinic acetylcholine receptor (alpha-7 nAChR) and act as positive allosteric modulators with or without allosteric agonist activity. The compounds are useful in diagnosing, preventing, or treating a variety of disorders involving cognition, learning, memory, neurodegeneration, drug addiction, inflammation, chronic pain, and neuropathic pain. The compounds also can be used to enhance memory and learning in normal individuals.

The invention claimed is: 
     
       1. A compound having one of the following formulas: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein the compound binds to an alpha-7 nicotinic acetylcholine receptor. 
       
     
     
       2. The compound of  claim 1  which is substantially enantiomerically pure. 
     
     
       3. The compound of  claim 1 , wherein the compound comprises one or more of  18 F,  19 F,  75 Br,  76 Br,  123 I,  124 I,  125 I,  131 I,  11 C,  13 C,  13 N,  15 O, or  3 H. 
     
     
       4. A radiolabeled compound of  claim 3 , or a pharmaceutically acceptable salt, hydrate, or solvate thereof, and an excipient. 
     
     
       5. The compound of  claim 1 , wherein the compound is a positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor. 
     
     
       6. The compound of  claim 1 , wherein the compound is an allosteric agonist of the alpha-7 nicotinic acetylcholine receptor. 
     
     
       7. The compound of  claim 1 , wherein the compound is capable of improving cognitive function, learning, and/or memory deficit. 
     
     
       8. The compound of  claim 1 , wherein the compound is capable of reducing inflammation. 
     
     
       9. The compound of  claim 1 , wherein the compound is capable of reducing neuropathic pain or pain related to a cognitive disorder. 
     
     
       10. A pharmaceutical composition comprising a compound of  claim 1 , or a pharmaceutically acceptable salt, hydrate, or solvate thereof, and an excipient.